In the past few decades, various chemical and physical strategies
have been explored to facilitate permeability of the skin and
enhance transportation of the macromolecules across the skin,
such as chemical enhancers [7], iontophoresis [8], sonophoresis
[9], microneedle [10], and electroporation [11]. Among these
technologies, electroporation, which has been explored to achieve
nucleic acid transfection for several decades, utilizes short electric
pulses to cause temporary nanoscale pores on the membrane to
alter the permeability. Due to its high efficiency, versatility, low cost,
and biochemical and biological nontoxicity [12], in vivo skin electroporation has been proved a feasible drug delivery technique for
DNA vaccination [5, 13], electrochemotherapy [14] and other
clinic applications. The electrodes used in in vivo electroporation
can be divided into two categories, invasive and noninvasive. The
noninvasive electrode is more popular in skin electroporation for its
low cost and slight mechanical injury on tissue. But since that the
stratum corneum has orders of magnitude higher electrical resistance than the hypodermal tissues, the electrical field may be concentrated within the high-resistance stratum corneum and
superficial layer leading to the high-voltage procedure. In contrast,
the invasive electrode, usually coupled with needles on the electrode head, may constrain the electric field across the stratum
corneum to generate sufficient filed in deep tissue with low voltage
pulse. Owing to microfabrication technology applied on biomedical engineering, severe tissue damage and pain can be avoided by
closely spaced and tiny microneedle electrodes with the dimension
ranging in a few hundred microns [15]. Besides, the small space
means the user can generate a sufficient electrical field with low
voltage pulses. On the other hand, the flexible microelectrode can
carry out a good coverage of irregularity skin surface and low
voltage electroporation. Despite of numerous advantages of these
microfabrication-based electrodes, clinic applications of such
devices have been received less attention due to the complicated
fabrication and high cost.
To address these challenges on the invasive approach, we previously proposed a novel strategy with the combined use of a commercial microneedle roller and a flexible interdigitated
electroporation array (FIEA) to achieve efficient and low-cost skin
electroporation of nucleic acid drugs [16]. Previous articles have
demonstrated combinations of disparate chemical and physical
approached cold be more effective compared to either alone in
terms of improving transdermal delivery efficiency and safety
[1, 17]. Here, the combination of punching by microneedle roller
and electroporation by flexible microelectrode can obviously facilitate the performance of the delivery and efficiently reduce the cost.
As shown in Fig. 1, the microneedle roller, a type of commercial,
low-priced and at-home device, is applied to pretreat the skin with
the delicate needles gently and painlessly piercing through the
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Dong Huang et al.
have been explored to facilitate permeability of the skin and
enhance transportation of the macromolecules across the skin,
such as chemical enhancers [7], iontophoresis [8], sonophoresis
[9], microneedle [10], and electroporation [11]. Among these
technologies, electroporation, which has been explored to achieve
nucleic acid transfection for several decades, utilizes short electric
pulses to cause temporary nanoscale pores on the membrane to
alter the permeability. Due to its high efficiency, versatility, low cost,
and biochemical and biological nontoxicity [12], in vivo skin electroporation has been proved a feasible drug delivery technique for
DNA vaccination [5, 13], electrochemotherapy [14] and other
clinic applications. The electrodes used in in vivo electroporation
can be divided into two categories, invasive and noninvasive. The
noninvasive electrode is more popular in skin electroporation for its
low cost and slight mechanical injury on tissue. But since that the
stratum corneum has orders of magnitude higher electrical resistance than the hypodermal tissues, the electrical field may be concentrated within the high-resistance stratum corneum and
superficial layer leading to the high-voltage procedure. In contrast,
the invasive electrode, usually coupled with needles on the electrode head, may constrain the electric field across the stratum
corneum to generate sufficient filed in deep tissue with low voltage
pulse. Owing to microfabrication technology applied on biomedical engineering, severe tissue damage and pain can be avoided by
closely spaced and tiny microneedle electrodes with the dimension
ranging in a few hundred microns [15]. Besides, the small space
means the user can generate a sufficient electrical field with low
voltage pulses. On the other hand, the flexible microelectrode can
carry out a good coverage of irregularity skin surface and low
voltage electroporation. Despite of numerous advantages of these
microfabrication-based electrodes, clinic applications of such
devices have been received less attention due to the complicated
fabrication and high cost.
To address these challenges on the invasive approach, we previously proposed a novel strategy with the combined use of a commercial microneedle roller and a flexible interdigitated
electroporation array (FIEA) to achieve efficient and low-cost skin
electroporation of nucleic acid drugs [16]. Previous articles have
demonstrated combinations of disparate chemical and physical
approached cold be more effective compared to either alone in
terms of improving transdermal delivery efficiency and safety
[1, 17]. Here, the combination of punching by microneedle roller
and electroporation by flexible microelectrode can obviously facilitate the performance of the delivery and efficiently reduce the cost.
As shown in Fig. 1, the microneedle roller, a type of commercial,
low-priced and at-home device, is applied to pretreat the skin with
the delicate needles gently and painlessly piercing through the
102
Dong Huang et al.